Lifespan gene in mice could help restrict old age diseases

Sunday 21 October 2007 19.13 EDT
First published on Sunday 21 October 2007 19.13 EDT

Scientists have found a gene that regulates lifespan in mammals which could one day lead to treatments to hold off ageing and its related illnesses such as Alzheimer's, cancer and heart disease.

Experiments in male mice showed that those without a gene called IRS-1 lived 20% longer and had much healthier lives. Female mice without the gene had even better longevity, living 30% longer on average. In addition to longer lives, the mice without IRS-1 were much healthier than normal mice as they aged - they had brighter eyes, better immune function and healthier skin and bones.

Dominic Withers, of the Centre for Research on Ageing at University College London, who led the study, said: "These results suggest that IRS-1 is a pathway conserved by evolution that regulates the lifespan of mammals, and it may point to methods of potentially delaying ageing in humans."

IRS-1 is involved in regulating the function of insulin, a hormone that controls the amount of sugar in the blood. Prof Withers' results, published online in the Faseb journal, add to a growing body of scientific work which points to a link between the genes that regulate insulin and how an animal ages. Similar genes in fruit flies and worms have already been linked to extended lifespan.

David Gems, another of the study's authors, said the work on IRS-1 in mice was the first to show that mammals could stay healthy as they lived longer. "In these animals we see delay in the onset of age-related illnesses such as osteoporosis, diabetes and immune dysfunction. Obviously, it's much harder to study these mechanisms in humans because our life expectancy is so much longer, but this study and our other work on ageing are laying crucial scientific groundwork."

Prof Withers is not yet certain why removing IRS-1 led to a longer life in mice. "Probably the reason why it works is that if you give the animal a little bit of stress, that's good - you switch on the pathways that protect from stress, cellular stress and damage."

He likened the effect to endurance training in athletes. "Running several miles day in, day out is probably quite stressful. But it then means that, over time, you can run lots of miles and it hurts you less."

If scientists find a way to manipulate the IRS-1 gene in humans, the results could provide great medical benefits. "Ageing is a major risk-factor for all diseases, heart disease, cancer, Alzheimer's," said Prof Withers. "Intervening in the ageing process may capture and ameliorate a wide range of diseases."

But he said the research would take another 10years of work in mouse models before the lessons could be transferred to humans. There were still some disadvantages to manipulating IRS-1 - the modified mice were 50% smaller than normal mice, for example.